Recent investigation of the mammalian esophagus has demonstrated that the stratified squamous epithelium of this organ transports water and electrolytes. This research proposes to: (1) define the normal physiology of transport by this epithelium, (2) investigate the hypothesis that abnormalities of transport play an important role in the pathophysiology of esophagitis and, (3) determine if the esophageal transmural electrical potential difference, which is a manifestation of electrolyte transport by this organ, is useful in the evaluation of human esophageal disease. Water and electrolyte transport will be investigated in vivo with the perfusion-water marker technique, and investigated in vitro by isotopic electrolyte flux determinations in the short-circuited epithelium with the Ussing chamber technique. The potential difference in the human esophagus will be measured at the time of esophageal manometric studies in patients with a wide variety of esophageal mucosal and muscular disorders, and the potential differences correlated with the type and severity of the disease as determined by traditional clinical investigative techniques. The characteristics of both active and passive transport will be defined in the esophagus of several animal species, including man. The neurohumoral control of transport will be determined by measuring the effects of cholinergic and adrenergic drugs, and of various hormones such as pitressin, aldosterone, gastrin, secretin, and cholecystokinin. These studies will elucidate an entirely new area of gastrointestinal physiology. The role of transport in the prevention or development of esophagitis will be explored by determining the effects of hydrochloric acid and/or bile salts and acetylsalicyclic acid on the active and passive transport characteristics of this epithelium. The changes in transport will be correlated with light and electron microscopic definitions of structure. These studies at the cellular level promise new insights into the pathophysiologic mechanisms responsible for this disease.